Reversible Subclinical Hypothyroidism in the Presence of Adrenal Insufficiency

Hussein D. Abdullatif, MD; Ambika P. Ashraf, MD

Disclosures

Endocr Pract. 2006;12(5):572-575. 

In This Article

Discussion

Cortisol deficiency can manifest with nonspecific and insidious symptoms, such as fatigue, weakness, listlessness, orthostatic dizziness, weight loss, and anorexia (6), and patients with hypothyroidism often have many of these symptoms. The mineralocorticoid function was intact in one of our patients (case 3), and all 3 patients had normal electrolytes. At the same time, they exhibited mild disruptions of thyroid function, mild reduction in FT4, and mild elevation in TSH, coexistent with adrenal insufficiency. Autoimmunity is a tenable explanation for thyroid dysfunction in one patient (case 2); however, the transient nature of the phenomenon does not support this argument. The first patient tested negative for the standard anti-thyroid and anti-adrenal antibodies. Allegedly, the stimulation of hypothalamic hormones by the regulatory influence of hypocortisolemia may result in elevation of the TSH level. Nevertheless, the low FT4 level in all 3 patients suggests that this phenomenon is not related to alterations in the hypothalamic release of corticotropinreleasing hormone and thyrotropin-releasing hormone.

An extensive review of the literature shed further light on this issue.[7,8,9,10,11,12] Gharib et al[7] and Topliss et al[8] described adolescent and adult patients with Addison's disease who had hypothyroidism at presentation and who became euthyroid after the initiation of corticosteroid treatment. In those reports, some of the patients with adrenal insufficiency had elevated TSH in conjunction with normal thyroxine (T4) levels, whereas others had low T4 values, and a third group had normal levels of TSH and T4. Both of these studies, however, were performed at a time when ultrasensitive TSH and FT4 assays were not available. On the contrary, the effect of adrenalectomy on the hypothalamic-pituitary-thyroid axis in rats revealed an increase in thyrotropin-releasing hormone, TSH, T4, and triiodothyronine (T3) levels in plasma from the 3rd to the 7th days after the procedure.[10] It is unclear what would have been the long-term outcome of FT4 levels if the study had been continued for a longer period. Other studies on adrenalectomized rats suggest the existence of a complex interaction among the thyroid hormones, glucocorticoids, catecholamines, and opioids that needs additional investigation for further clarification.[13] A patient with obesity attributable to pro-opiomelanocortin deficiency was reported to have high TSH levels and low T4 levels as well;[12] this finding suggests further complexities in the thyroadrenal interactions.

Why some patients with adrenal insufficiency manifest reversible hypothyroidism is unclear. Certain reports have suggested that corticosteroid therapy causes some immune modulation and hence decreases the autoimmune activity in Hashimoto's thyroiditis.[14] Other investigators have postulated that patients with high TSH concentrations or anti-TPO antibodies have a subclinical thyroid disease that worsens when subjected to a low steroid environment.[15] This premise suggests some immune modulation by glucocorticoids, even at maintenance doses. De Nayer et al[16] suggested a decrease in the interaction between T3 and its nuclear receptors in corticosteroid deficiency states. Perhaps there is impaired sensitivity of the thyroid gland to TSH in hypocortisolemic states that alters thyroid hormone secretion, or perhaps there is a stimulation in deiodination from T4 to T3 and reverse T3. It is also possible that, by lowering the thyroid hormone production, the body might be reducing the metabolism in hypocortisolemic states.

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